Diagnosis and Management of Lymphatic Disorders in Congenital Heart Disease

Abstract Purpose of Review Lymphatic disorders have received an increasing amount of attention over the last decade. Sparked primarily by improved imaging modalities and the dawn of lymphatic interventions, understanding, diagnostics, and treatment of lymphatic complications have undergone considerable improvements. Thus, the current review aims to summarize understanding, diagnostics, and treatment of lymphatic complications in individuals with congenital heart disease. Recent Findings The altered hemodynamics of individuals with congenital heart disease has been found to profoundly affect morphology and function of the lymphatic system, rendering this population especially prone to the development of lymphatic complications such as chylous and serous effusions, protein-losing enteropathy and plastic bronchitis. Summary Although improved, a full understanding of the pathophysiology and targeted treatment for lymphatic complications is still wanting. Future research into pharmacological improvement of lymphatic function and continued implementation of lymphatic imaging and interventions may improve knowledge, treatment options, and outcome for affected individuals. </jats:sec

Gravity and lymphodynamics

The lymphatic system is compromised in different groups of patients. To recognize pathology, we must know what is healthy. We use Near‐Infrared Fluorescence (NIRF) to assess peripheral lymphatic function in humans. We have shown that external factors such as exercise, hyperthermia, and pharmacological mediators influence the function of peripheral lymphatic vessels. In this study, we explored the impact on lymphatic vessels by the ever‐present external factor—gravity. We used NIRF imaging to investigate the lymphatic changes to gravity. Gravity was assessed by changing body position from supine to standing. We extracted following lymphatic functional parameters: lymphatic packet propulsion frequency (contractions/min), velocity (cm/s), and pressure (mmHg). Raw data analysis was performed using a custom‐written Labview program. All sequences were analyzed by two observers and interclass correlation scores were calculated. All statistical analysis was performed using RStudio Team (2021). RStudio: Integrated Development Environment for R. RStudio, PBC. Healthy participants (n = 17, 11 males, age 28.1 ± 2.6 years) were included. The lymphatic packet propulsion frequency at baseline was 0.5 ± 0.2 contractions/min and rose within 3 min significantly to a maximum of 1.2 ± 0.5 contractions/min during upright posture and remained significantly higher than the baseline lymphatic packet propulsion frequency after lying down again for up to 6 min. The lymph velocity was 1.5 ± 0.4 cm/s at baseline and changed in both directions and without a specific pattern at different points in time during standing. Lymph pressure was significantly higher while standing (mean increase 9 mmHg, CI: 2–15 mmHg). The ICC scores were 89.8% (85.9%–92.7%), 59.3% (46.6%–69.6%) and 89.4% (79.0%–94.8%) in lymphatic packet propulsion frequency (130 observations), velocity (125 observations), and pressure (30 observations), respectively. The lymphatic system responds within few minutes to gravitational changes by increasing lymphatic packet propulsion frequency and pressure

Lymphatic Function Decreases over Time in the Arms of Breast Cancer Patients following Treatment

In patients with breast cancer-related lymphedema, distinct lymphatic patterns and changed lymphatic contractile function have been described, but it is unknown how these characteristics change over time and to what extent they appear before clinical edema is detectable. Recently, we described the lymphatic morphology and function in a cohort of breast cancer patients shortly after radiation therapy (RT). In the current study, we investigate lymphatic function and morphology in the same cohort after 1 year of follow-up. METHODS: The study population consisted of 28 breast cancer patients investigated 12 months after adjuvant locoregional RT. Lymphatic contraction frequency (CF), propulsion velocity, and the morphology of lymphatic vessels in the upper extremities were described in vivo using near-infrared fluorescence imaging. Lymphatic stress test was performed using hyperthermia. RESULTS: At 1 year after RT, (n = 28) 46% of the patients presented with lymphatic morphological abnormalities with a degree of dermal backflow and 21% had developed clinical breast cancer-related lymphedema. In the ipsilateral arm, CF was 23% lower than in the contralateral arm (P = 0.04). Since primary examination, CF in the ipsilateral arm decreased by 40% (P = 0.03), whereas no change was observed in the contralateral arm. During hyperthermia, the ipsilateral arms with lymphatic complications were not able to increase CF as the remaining subgroups. CONCLUSIONS: Lymphatic function in the ipsilateral arm deteriorated over time after adjuvant breast cancer therapy. Furthermore, the presence of abnormal torturous lymphatic vessels in asymptomatic arms appeared to be associated with weak lymphatic reserve pumping capacity